This epidemiological study aims to: (1) determine the cumulative 15-year progression of diabetic retinopathy and incidence of proliferative retinopathy, macular edema, visual impairment, other microvascular (diabetic nephropathy) and macrovascular (myocardial infarction, lower extremity amputation) complications in persons with type I diabetes and quantify the risk of these outcomes with regard to markers of inflammation, endothelial dysfunction, cellular adhesion and of estimated insulin resistance; (2) examine the association of change in visual acuity and changes in self-rated health and self-reported visual-targeted quality of life in type 1 persons with long term diabetes over a ten year period; and (3) examine the cross-sectional association of visual impairment and depression in persons with type 1 diabetes. The study builds upon the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR, NEIR01 03083) which included all insulin-taking persons with type 1 diabetes and who were receiving primary medical care in an 11-county area of southwestern Wisconsin in 1979-1980. Exams were performed in 1980-82, 1984-86, 1990-92, 1995-96, and 2000-01. These persons will be examined in their communities in a mobile examining van. Refraction, visual acuity, intraocular pressure, blood pressure and other measurements will be obtained according to standardized protocols. Objective recording of retinopathy from stereoscopic fundus photography combined with a standardized grading will be used. Standardized questionnaires including the SF-36, the NEI-VFQ 25, and the Center for Epidemiologic Studies Depression Scale (CES-D) will be administered. C-reactive protein, interleukin-6, tumor necrosis factor-"c, and other markers of inflammation, endothelial dysfunction, and cellular adhesion will be measured. New data from this study will provide a unique opportunity to evaluate the relationship of new factors to the presence and severity of retinopathy and to the progression of retinopathy and incidence of other micro- vascular (e.g., diabetic nephropathy) and macrovascular (e.g., lower extremity amputation, myocardial infarction) complications and will provide needed information regarding the associations of retinopathy and visual impairment to self-reported visual-targeted quality of life and depression in persons with long duration of type 1 diabetes. These data will be useful to patients and their physicians involved in the management of diabetes and to public health practitioners designing and delivering preventive care services. Conversely, the new data to be collected in this study may provide insights into the relative protective value of low levels of markers of inflammatory, cell adhesion, and endothelial dysfunction on vascular complications of diabetes mellitus.